SELECTIVE elimination of disease driving cells in myelofibrosis by CART T cell therapy observed in new preclinical research investigating a personalised treatment approach for patients with myeloproliferative neoplasms. The engineered immune cells were designed to recognise mutations in the CALR gene, which are present in around one third of patients with these chronic blood cancers. Findings from laboratory models, patient samples, and mouse studies suggest that this targeted strategy could offer a more precise therapeutic option for patients with limited curative treatment choices.
CAR T Cell Therapy Targets Disease Driving Cells
Myeloproliferative neoplasms are chronic blood cancers that develop following the acquisition of a mutation in a blood stem cell. The personalised CAR T cell therapy was engineered to identify cells carrying mutant CALR. Across patient samples, laboratory models replicating human bone marrow, and mouse studies, the engineered immune cells selectively eliminated cancer cells expressing the mutation while sparing healthy blood cells. These findings indicate that the therapy can distinguish between malignant and normal cells, an important consideration for future clinical development.
Bone Marrow Models Demonstrate Therapeutic Potential
Researchers also evaluated the therapy using three-dimensional laboratory grown bone marrow organoids seeded with myelofibrosis cells. These models were designed to reproduce the fibrotic tissue environment characteristic of advanced disease, providing a clinically relevant setting in which to assess immune cell activity.
Within these organoids, the engineered cells successfully migrated into heavily scarred tissue and eliminated mutant cancer cells. According to the investigators, this finding suggests that fibrosis may not prevent immune cells from reaching their intended targets, supporting the potential feasibility of this approach in patients with advanced disease.
Future Clinical Development
Although myeloproliferative neoplasms are classified as rare diseases, approximately 4,000 people receive a diagnosis in the United Kingdom each year, with mutations in CALR accounting for around one third of cases. Many more people are already living with these conditions.
The research team is now seeking funding to support a first in human clinical trial. If early clinical findings prove encouraging, the investigators hope that this personalised CAR T cell therapy could become a safer and more effective immunotherapy for patients with myelofibrosis and potentially other blood cancers. While these results remain preclinical, they provide important evidence supporting further clinical evaluation of this targeted treatment strategy.
Reference
Radcliffe Department of Medicine. New personalised therapy targets chronic blood cancer. 2026. Available at: https://www.rdm.ox.ac.uk/news/new-personalised-therapy-targets-chronic-blood-cancer. Last accessed: 14 July 2026.
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